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Elucidating the role of muscarinic receptors in psychosis

Data from clinical, postmortem, neuroimaging, and preclinical and clinical pharmacology studies support this hypothesis.

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The binding of ACh to the nicotinic receptor leads to an activation of the ion channel, resulting in a rapid inflow of sodium ions.Animal studies—genetically modified animals studies, in particular—have helped clarify the physiological role of the different mus-carinic receptor subtypes.The muscarinic hypothesis of schizophrenia The muscarinic hypothesis of schizophrenia postulates that the muscarinic ACh system plays a crucial role in the pathology and treatment of schizophrenia.Therefore, research has also focused on the role of other neurotransmitter systems, including glutamate, g-aminobutyric acid, serotonin, and acetylcholine (ACh) in schizophrenia.This review focuses on the muscarinic hypothesis of schizophrenia and the potential implications of ACh for the treatment of schizophrenia.Some of these approaches have been applied to schizophrenia and represent promising novel targets for its pharmacological treatment.

Cholinesterase inhibitors Cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) increase the intrasynaptic concentration of ACh through inhibition of the enzyme acetylcholinesterase.

Acetylcholine as a neurotransmitter For almost a century, ACh has been recognized as a neurotransmitter both in the CNS and in the peripheral nervous system (PNS).

ACh plays a crucial role in a variety of CNS and PNS functions, including sensory perception, motor function, cognitive processing, memory, arousal, attention, sleep, nociception, motivation, reward, mood, psychosis, and neuroplasticity.

In contrast, muscarinic ACh receptors are G-protein-coupled receptors.

The activation of muscarinic receptors results in a slow- er but potentially more sustained response.

Cholinergic neurons in the brain Most cholinergic projection neurons are located in the basal forebrain and the brain stem.